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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | GPR133-Gain-miniG13 complex | |||||||||
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![]() | GPCR / G12/G13 / Complex / Stachel / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() D5 dopamine receptor binding / regulation of skeletal muscle contraction / regulation of fibroblast migration / Rho-activating G protein-coupled receptor signaling pathway / regulation of small GTPase mediated signal transduction / NRAGE signals death through JNK / branching involved in blood vessel morphogenesis / CDC42 GTPase cycle / regulation of postsynapse assembly / Rho protein signal transduction ...D5 dopamine receptor binding / regulation of skeletal muscle contraction / regulation of fibroblast migration / Rho-activating G protein-coupled receptor signaling pathway / regulation of small GTPase mediated signal transduction / NRAGE signals death through JNK / branching involved in blood vessel morphogenesis / CDC42 GTPase cycle / regulation of postsynapse assembly / Rho protein signal transduction / RAC1 GTPase cycle / guanyl-nucleotide exchange factor activity / brush border membrane / G protein-coupled receptor activity / platelet activation / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / regulation of blood pressure / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / melanosome / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / regulation of cell shape / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / G protein activity / GTPase binding / Ca2+ pathway / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / in utero embryonic development / Ras protein signal transduction / cell differentiation / Extra-nuclear estrogen signaling / cell surface receptor signaling pathway / cell population proliferation / postsynapse / nuclear speck / G protein-coupled receptor signaling pathway / lysosomal membrane / focal adhesion / GTPase activity / synapse / protein-containing complex binding / GTP binding / signal transduction / extracellular exosome / nucleoplasm / metal ion binding / nucleus / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.51 Å | |||||||||
![]() | Xi Y / Pu X / Ping Y | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM structural elucidation and molecular mechanism of the GPR133-G13 signaling complex. Authors: Xuanyu Pu / Yue-Tong Xi / Meng-Xin Wang / Daolai Zhang / Yu-Qi Ping / Peng Xiao / Jin-Peng Sun / ![]() Abstract: GPR133 is an adhesion-class G protein-coupled receptor (GPCR) that has recently been de-orphanized. Its functions are complex and multifaceted. While GPR133 is primarily recognized for coupling with ...GPR133 is an adhesion-class G protein-coupled receptor (GPCR) that has recently been de-orphanized. Its functions are complex and multifaceted. While GPR133 is primarily recognized for coupling with the Gs subunit to mediate elevated intracellular cAMP levels, its potential engagement with alternative signaling pathways remains poorly characterized. In our experiments, we demonstrated that GPR133 exhibits constitutive self-activation via its Stachel sequence as an adhesion GPCR, enabling activation of downstream G13 signaling. We reconstituted the GPR133-GAIN-miniGα13 complex in vitro and resolved its cryo-electron microscopy structure at a resolution of 3.51 Å. Detailed structural comparisons between the GPR133-GAIN-miniGα13 complex and the previously resolved GPR133-CTF-Gs structure highlighted both conserved and different features. These findings provide critical insights into the signal transduction mechanisms of GPR133 and lay a foundation for targeted therapeutic strategies. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 52.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.1 KB 18.1 KB | Display Display | ![]() |
Images | ![]() | 34.9 KB | ||
Filedesc metadata | ![]() | 6.2 KB | ||
Others | ![]() ![]() | 55.4 MB 55.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 837 KB | Display | ![]() |
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Full document | ![]() | 836.6 KB | Display | |
Data in XML | ![]() | 11.9 KB | Display | |
Data in CIF | ![]() | 14.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9v0uMC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.93 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_64672_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_64672_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : GPR133-Gain-miniG13-Gbeta1-Ggamma2 complex
Entire | Name: GPR133-Gain-miniG13-Gbeta1-Ggamma2 complex |
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Components |
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-Supramolecule #1: GPR133-Gain-miniG13-Gbeta1-Ggamma2 complex
Supramolecule | Name: GPR133-Gain-miniG13-Gbeta1-Ggamma2 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Adhesion G-protein coupled receptor D1
Macromolecule | Name: Adhesion G-protein coupled receptor D1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 65.688828 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: HPIITNLTEE RKTFQSPGVI LSYLQNVSLS LPSKSLSEQT ALNLTKTFLK AVGEILLLPG WIALSEDSAV VLSLIDTIDT VMGHVSSNL HGSTPQVTVE GSSAMAEFSV AKILPKTVNS SHYRFPAHGQ SFIQIPHEAF HRHAWSTVVG LLYHSMHYYL N NIWPAHTK ...String: HPIITNLTEE RKTFQSPGVI LSYLQNVSLS LPSKSLSEQT ALNLTKTFLK AVGEILLLPG WIALSEDSAV VLSLIDTIDT VMGHVSSNL HGSTPQVTVE GSSAMAEFSV AKILPKTVNS SHYRFPAHGQ SFIQIPHEAF HRHAWSTVVG LLYHSMHYYL N NIWPAHTK IAEAMHHQDC LLFATSHLIS LEVSPPPTLS QNLSGSPLIT VHLKHRLTRK QHSEATNSSN RVFVYCAFLD FS SGEGVWS NHGCALTRGN LTYSVCRCTH LTNFAILMQV VPLELARGHQ VALSSISYVG CSLSVLCLVA TLVTFAVLSS VST IRNQRY HIHANLSFAV LVAQVLLLIS FRLEPGTTPC QVMAVLLHYF FLSAFAWMLV EGLHLYSMVI KVFGSEDSKH RYYY GMGWG FPLLICIISL SFAMDSYGTS NNCWLSLASG AIWAFVAPAL FVIVVNIGIL IAVTRVISQI SADNYKIHGD PSAFK LTAK AVAVLLPILG TSWVFGVLAV NGCAVVFQYM FATLNSLQGL FIFLFHCLLN SEVRAAFKHK TKVWSLTSSS ARTSNA KPF HSDLMNGTRP GMASTKLSPW DKSSHSAHRV DLSAV UniProtKB: Adhesion G-protein coupled receptor D1 |
-Macromolecule #2: Guanine nucleotide-binding protein subunit alpha-13,Isoform 2 of ...
Macromolecule | Name: Guanine nucleotide-binding protein subunit alpha-13,Isoform 2 of Guanine nucleotide-binding protein subunit alpha-13 type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 26.705596 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MMGSTVSAED KAAAERSKEI DKCLSREKTY VKRLVKILLL GADNSGKSTF LKQMRIIHGG SGGSGGTKGI HEYDFEIKNV PFKMVDVGG QRSERKRWFE CFDSVTSILF LVDSSDFNRL TESLNDFETI VNNRVFSNVS IILFLNKTDL LEEKVQIVSI K DYFLEFEG ...String: MMGSTVSAED KAAAERSKEI DKCLSREKTY VKRLVKILLL GADNSGKSTF LKQMRIIHGG SGGSGGTKGI HEYDFEIKNV PFKMVDVGG QRSERKRWFE CFDSVTSILF LVDSSDFNRL TESLNDFETI VNNRVFSNVS IILFLNKTDL LEEKVQIVSI K DYFLEFEG DPHCLRDVQK FLVECFRNKR RDQQQKPLYH HFTTAINTEN ARLIFRDVKD TILHDNLKQL MLQ UniProtKB: Guanine nucleotide-binding protein subunit alpha-13, Guanine nucleotide-binding protein subunit alpha-13, Guanine nucleotide-binding protein subunit alpha-13 |
-Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 37.784301 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: GSLLQSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHLA KIYAMHWGTD SRLLVSASQD GKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN LKTREGNVRV SRELAGHTGY LSCCRFLDDN Q IVTSSGDT ...String: GSLLQSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHLA KIYAMHWGTD SRLLVSASQD GKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN LKTREGNVRV SRELAGHTGY LSCCRFLDDN Q IVTSSGDT TCALWDIETG QQTTTFTGHT GDVMSLSLAP DTRLFVSGAC DASAKLWDVR EGMCRQTFTG HESDINAICF FP NGNAFAT GSDDATCRLF DLRADQELMT YSHDNIICGI TSVSFSKSGR LLLAGYDDFN CNVWDALKAD RAGVLAGHDN RVS CLGVTD DGMAVATGSW DSFLKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |